在日本和白种人健康受试者中，作为吸入固定剂量复方制剂给予的吲达特罗、格隆溴铵和糠酸莫米松的药代动力学。
Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects.
机构信息
Novartis Pharma KK, Tokyo, Japan.
Novartis Institutes for BioMedical Research, Cambridge, USA.
出版信息
BMC Pulm Med. 2021 Jan 7;21(1):18. doi: 10.1186/s12890-020-01382-6.
BACKGROUND
A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d.
METHODS
This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 μg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14.
RESULTS
In total, 16 Japanese (median age 31 years [range 20-40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21-43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for C for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed.
CONCLUSION
Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups.
TRIAL REGISTRATION
Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.
背景
通过 Breezhaler 装置每日一次（o.d.）给予的固定剂量的乙酰谷氨酰胺（IND）、格隆溴铵（GLY）和糠酸莫米松（MF）联合制剂（IND/GLY/MF）正在开发用于治疗哮喘。这项研究比较了日本和高加索男性受试者在接受 IND/GLY/MF o.d. 多次吸入后，IND、GLY 和 MF 的稳态药代动力学。
方法
这是一项单中心、开放标签、2 治疗交叉研究，洗脱期为 21 天。日本和高加索受试者在每个时期接受 IND/GLY/MF 150/50/80μg（吸入性皮质类固醇[ICS]中剂量）或 150/50/160μg o.d.（ICS 高剂量）治疗 14 天。在第 1 天和第 14 天给药后 24 小时内对药代动力学进行了特征描述。
结果
共纳入 16 名日本受试者（中位年龄 31 岁[范围 20-40 岁]，平均体重 68.3kg）和 17 名高加索受试者（中位年龄 27 岁[范围 21-43 岁]，平均体重 75.0kg）被随机分组。第 14 天高 ICS 剂量时，IND、GLY 和 MF 的几何均数比值（日本/高加索）[90%置信区间（CI）]分别为 1.31[1.13, 1.51]、1.38[1.13, 1.69]和 1.07[0.969, 1.18]。第 14 天高 ICS 剂量时，IND、GLY 和 MF 的 AUC 几何均数比值（日本/高加索）[90%CI]分别为 1.17[1.01, 1.35]、1.05[0.920, 1.20]和 1.15[1.05, 1.27]。中 ICS 剂量治疗时，所有成分均呈现出相似的趋势。IND/GLY/MF 是安全且耐受良好的；未观察到疑似与研究药物相关的不良事件。
结论
作为固定剂量联合使用时，IND、GLY 和 MF（高剂量和中剂量）的药代动力学在日本和高加索受试者之间具有可比性。在这两个种族群体中，以给予的剂量给予 IND/GLY/MF 联合用药是安全且耐受良好的。
试验注册
日本临床试验注册：jRCT2031200227，于 2020 年 12 月 4 日回顾性注册。
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